Scholarlink

<p>Suspected infection requiring hospitalisation has highly heterogenous presentation. Yet, variances in host response and its implications are largely unknown. In this multicentre cohort of 3802 individual patients presenting to the Emergency Department (ED) with suspected infection requiring hospitalisation, we apply uniform manifold approximation and projections and K-means clustering to 29 plasma proteins to identify biologically discrete host response clusters. In this work, we first describe two large clusters, called “Dysregulated” and “Undifferentiated”, with abnormal protein concentrations and adverse outcomes in the former. Through further clustering, we identify 4 sub-clusters in the Dysregulated cluster, each with discrete biological signatures, clinical correlates, and outcomes. Clusters 3 and 4 are characterised by renal impairment and viral infections respectively. Clusters 5 and 6 are associated with bacterial culture positivity, with the former consistent with an immunosuppressed signature and worse outcomes, and the latter with gram-negative bacteria, higher IL-6 and IL-8, and better outcomes despite higher vasopressor use. These clusters are a biologically driven approach to characterising acute suspected infection and may lead to more targeted therapeutics.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Multivariate protein landscape of host response in hospitalised patients with suspected infection in the emergency department

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月22日

查看全文
  • Pratik Sinha,
  • Alexandra B. Spicer,
  • Sivasubramanium Bhavani,
  • Carlos López-Espina,
  • Gregory L. Watson,
  • Akhil Bhargava,
  • Lee Schmalz,
  • Shah Khan,
  • Matthew D. Sims,
  • Ashok V. Palagiri,
  • Alon Dagan,
  • Karthik V. Iyer,
  • Matthew J. Crisp,
  • Carmen DeMarco,
  • Alexandra Halalau,
  • Nicholas Maddens,
  • Niko Kurtzman,
  • Deesha Sarma,
  • Falgun Gosai,
  • Anwaruddin Syed,
  • Saleem Azad,
  • Aimee Espinosa,
  • Francisco Davila,
  • Hugo Davila,
  • Neil Shadbeh Evans,
  • Scott Smith,
  • Bobby Reddy Jr,
  • Philip A. Verhoef,
  • Matthew M. Churpek

摘要

Suspected infection requiring hospitalisation has highly heterogenous presentation. Yet, variances in host response and its implications are largely unknown. In this multicentre cohort of 3802 individual patients presenting to the Emergency Department (ED) with suspected infection requiring hospitalisation, we apply uniform manifold approximation and projections and K-means clustering to 29 plasma proteins to identify biologically discrete host response clusters. In this work, we first describe two large clusters, called “Dysregulated” and “Undifferentiated”, with abnormal protein concentrations and adverse outcomes in the former. Through further clustering, we identify 4 sub-clusters in the Dysregulated cluster, each with discrete biological signatures, clinical correlates, and outcomes. Clusters 3 and 4 are characterised by renal impairment and viral infections respectively. Clusters 5 and 6 are associated with bacterial culture positivity, with the former consistent with an immunosuppressed signature and worse outcomes, and the latter with gram-negative bacteria, higher IL-6 and IL-8, and better outcomes despite higher vasopressor use. These clusters are a biologically driven approach to characterising acute suspected infection and may lead to more targeted therapeutics.